Combating diabetes complications by 1-Fe, a corrole-based catalytic antioxidant.

Abstract

The potent corrole-based ROS/RNS decomposition catalyst 1-Fe was examined regarding its effect on the development of diabetes complications, in parallel with studies that addressed safety and toxicity issues that are crucial for forwarding the compound towards clinical trials. Cardiotoxicity and mutagenic potential were addressed by applying the hERG and AMES tests on 1-Fe, revealing that it is safe enough for further development. General toxicity studies in rats disclosed the appearance of mild adverse effect only at a dose of 300 mg/kg/day. In the streptozotocin-induced rat model of diabetes, 20 mg/kg/day 1-Fe prevented cataract incidents and reduced its severity, displayed a favorable effect on kidney function, and also decreased serum cholesterol and triglyceride levels. Comparisons with alpha lipoic acid, a compound with reported benefits in the same mouse model, indicate that the benefits of 1-Fe are due to the combination of its ability to disarm ROS/RNS and its positive effect on lipid profile.

• Authors: Adi Haber, Itzchak Angel, Atif Mahammed, Zeev Gross
• Journal: Journal of diabetes and its complications (J Diabetes Complications) 2013 Jul-Aug Vol. 27 Issue 4 Pg. 316-21 ISSN: 1873-460X [Electronic] United States
• PMID: 23602197 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Inc. All rights reserved.

Chemical References

• Antioxidants
• Metalloporphyrins
• Porphyrins
• corrole
• Streptozocin
• Thioctic Acid

Topics

• Animals
• Antioxidants (therapeutic use)
• CHO Cells
• Catalysis
• Cricetinae
• Cricetulus
• Diabetes Complications (prevention & control)
• Diabetes Mellitus, Experimental (chemically induced, complications, drug therapy)
• Drug Evaluation, Preclinical
• Female
• Male
• Metalloporphyrins (therapeutic use)
• Porphyrins (therapeutic use)
• Rats
• Rats, Sprague-Dawley
• Streptozocin
• Thioctic Acid (therapeutic use)